Beyond conventional 5-Fluorouracil: Recent medicinal chemistry strategies to enhance its anticancer efficacy

Area of Science:

• Medicinal Chemistry
• Oncology
• Drug Development

Background:

• 5-Fluorouracil (5-FU) is a widely used antimetabolite anticancer drug.
• 5-FU exhibits limitations including poor bioavailability, short half-life, and low tumor selectivity.
• These drawbacks hinder its efficacy in treating various solid tumors.

Purpose of the Study:

• To review medicinal chemistry strategies for overcoming 5-FU limitations.
• To comparatively analyze structural modifications of 5-FU, including analogs, hybrids, and prodrugs.
• To highlight emerging trends in 5-FU drug development over the past five years.

Main Methods:

• Comparative analysis of published literature on 5-FU modifications.
• Focus on structural modifications leading to analogs, hybrid compounds, and prodrugs.
• Evaluation of strategies addressing bioavailability, half-life, and selectivity.

Main Results:

• Mutual prodrugs emerge as a leading strategy to enhance 5-FU therapy.
• Structural modifications have yielded promising analogs, hybrids, and prodrugs.
• Evidence suggests prodrug approaches can mitigate 5-FU's clinical challenges.

Conclusions:

• Mutual prodrugs represent a key advancement in 5-FU-based cancer therapy.
• Future research should prioritize improved tumor targeting and translational potential of 5-FU derivatives.
• Medicinal chemistry offers viable solutions to enhance the therapeutic profile of 5-FU.